Action Points

A combination of pravastatin (Pravachol) plus ezetimibe (Zetia) given for 1 year improved endothelial function and the overall lipid profile in a small group of patients with systemic lupus erythematosus (SLE) who had impaired endothelial function at baseline.

Note that adverse treatment-related effects occurred in only one patient who reported abdominal pain and diarrhea 6 months after receiving the combination of pravastatin and ezetimibe.

A combination of pravastatin (Pravachol) plus ezetimibe (Zetia) given for 1 year improved endothelial function and the overall lipid profile in a small group of patients with systemic lupus erythematosus (SLE) who had impaired endothelial function at baseline, a study from Mexico has found.

After 12 months of lipid-lowering therapy, measures in flow-mediated vasodilatation (FMV) -- a reflection of underlying endothelial function -- increased by 140%, from a mean baseline value of 7.58% to 18.22% at 12 months, observed Olga Vera-Lastra, MD, of Hospital de Especialidades, Mexico City, and colleagues.

There was also a statistically significant 37% decrease in low-density lipoprotein (LDL) cholesterol levels from baseline to month 12 as well as a 21.3% improvement in total cholesterol (TC), Vera-Lastra and colleagues reported in Lupus.

"[Endothelial dysfunction] is the first step toward atherosclerosis [and] several studies have shown that ED measured by FMV is significantly impaired in patients with SLE, including those without cardiovascular risk factors," they wrote.

"Therefore, interventions that modify atherosclerosis risk factors may be of benefit in SLE patients."

Twenty-two patients with SLE for a mean duration of 10 years were included in the study. All participants attended the outpatient department of The Hospital de Especialidades Centro Medico Nacional La Raza between February 2010 and February 2011. A blood sample was taken after a 12-hour fast, and lipid fractions including TC, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides were measured, as was C-reactive protein (CRP).

After 12 months of the combination strategy, TC decreased from 200.39 mg/dL at baseline to 158.06 mg/dL (P<0.01) at study endpoint. LDL cholesterol in turn dropped from 125.78 mg/dL on study entry to 78.89 mg/dL 12 months later (P<0.001), while HDL cholesterol increased modestly and insignificantly from 49 mg/dL at study entry to 52.22 mg/dL at follow-up.

A significant decrease in CRP serum levels was similarly observed from a baseline level of 4.49 mg/L to 2.38 mg/L, a reduction of 2.11 mg/L (95% CI 0.980-3.32, P<0.002).

Adverse treatment-related effects occurred in only one patient who reported abdominal pain and diarrhea 6 months after receiving the combination of pravastatin and ezetimibe.

"When ED is not treated promptly in patients with SLE, it will evolve into [cardiovascular disease] such as ischemic cardiopathy or cerebral vascular disease," Vera-Lastra and colleagues wrote.

"For this reason, prevention is very important."

Study limitations include the small sample size and a relatively short follow-up of 1 year.

Experts have recommended that patients at high risk for CVD, which would include SLE patients, achieve a LDL cholesterol level below 70 mg/dL.

"Our patients ... achieved the goal of TC and LDL-C [cholesterol] recently published by the National Cholesterol Education Program Adult Treatment Panel (ATP IV)," the study authors pointed out.

According to the ATP IV, an LDL cholesterol level of less than 70 mg/dL represents an ideal treatment target, although an LDL cholesterol level of less than 100 mg/dL is also acceptable.

Robert Hegele, MD, of the Lipid Genetics Clinic at London Health Sciences Center in Ontario, told MedPage Today that it was interesting that the investigators chose to study pravastatin and ezetimibe as pravastatin was among the first statins to come online in the 1990s and as such, "it's not usually the first choice for most practitioners now in North America."

Moreover, had investigators used one of the more potent statins, "they would have had a bigger effect on LDL cholesterol and they might have seen a bigger effect on FMV as well," Hegele added.

On the other hand, the fact that the investigators still saw an effect from the combination therapy large enough to send a statistical signal over a very small sample size suggests that lipid-lowering therapy in this patient population could be worthwhile.

"FMV fits into the category of many traits we call surrogate markers," Hegele explained.

"So the study endpoint was a surrogate endpoint like carotid media thickness, and to be definitive and evidence-based, you really need to have an outcomes study done in this patient population to confirm that lipid-lowering therapy does improve cardiovascular outcomes with longer-term follow-up."

The authors declared no potential conflicts of interest and received no financial support for their research.

Hegele had no relevant financial conflicts of interest to declare.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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